The present invention relates to a method of preparing an implantable radioactive metallic medical device. More particularly, the present invention relates to a method of preparing a radioactive metallic stent for use in preventing restenosis in atherosclerotic coronary arteries that have been subjected to percutaneous transluminal coronary angioplasty, hereinafter referred to as "balloon angioplasty".
Atherosclerosis is a disease in which vascular lesions or plaques consisting of cholesterol crystals, necrotic cells, excess fiber elements and calcium deposits accumulate on the interior walls of an individual's arteries. The presence of such plaques in the artery leads to thickening and retraction of the artery. Eventually the enlargement of such plaques can lead to an occlusion of the lumen of the artery at the site of the lesion. One of the most successful procedures for treating the narrowing of the arteries caused by atherosclerosis is balloon angioplasty. Balloon angioplasty consists of introducing a deflated balloon into the atherosclerotic artery, placing the balloon adjacent the site of the plaque or atherosclerotic lesion, inflating the balloon to a pressure of approximately 6 to 20 atmospheres thereby "cracking" the plaque and increasing the cross-sectional area of the lumen of the artery.
Unfortunately, the pressure that is exerted on the plaque during balloon angioplasty also traumatizes the artery. Accordingly, in 30-40% of the cases the vessel either gradually renarrows or recloses at the locus of the original stenotic lesion. This gradual renarrowing or reclosure is referred to as restenosis. Studies of the mechanism of restenosis have shown that it is due in part to a proliferation of smooth muscle cells and in part to retraction or recoil of the blood vessels.
A number of approaches for preventing restenosis are currently being used or tested. One approach employs a metallic stent which is deployed at the site of the stenotic lesion following balloon angioplasty. Typically, metallic stents are made in the form of a mesh-like network of linked wires and open spaces. Metallic stents have the mechanical strength necessary to prevent recoil or retraction of the barotraumatized vessel. However, the metallic stents that are presently used do not prevent proliferation of the smooth muscle cells.
Animal studies have shown that the rate of restenosis can be further reduced by implanting radioactive metallic stents at the site of the atherosclerotic lesion following balloon angioplasty. The local irradiation supplied by such stents prevents smooth muscle cell proliferation. The use of such radioactive stents is currently being tested in a clinical phase I trial. The stents that are being used in these trials are loaded with .sup.32 P by ion implantation. This process involves the bombardment of rotating stents with .sup.32 P ions. The .sup.32 P ions become embedded in the metal surface to a depth of a few .mu.m.
Typically, .sup.32 P stents cannot be activated within the hospital. .sup.32 P stents must be activated in advance and then shipped to the hospital. Because of constant decay of the radioisotope, .sup.32 P stents may not be able to deliver the required dose to the site of the stenotic lesion if stored for any length of time at the hospital. Therefore, unless a hospital receives a fresh supply of .sup.32 P stents of various types, lengths and doses on a daily basis, a .sup.32 P stent that matches the individual lesion characteristics of the patient may not be available at the time of insertion. In addition, .sup.32 P stents deliver radiation to the area near the stent for more than 30 days after implantation. Radiobiological concerns make delivering the radiation over this length of time undesirable. Previous studies have shown that irradiation of the vessel within a few hours prior to and 3 days post angioplasty is the most desirable range of time for treatment. Thus, the length of time the patient is exposed to radiation from the .sup.32 P stents is excessive. Moreover, it is likely that .sup.32 P stents will deliver radioactivity to the target tissue at a dose rate of less than 10 centigray (cGy) per hour during most of the time the .sup.32 P stent delivers radioactivity. Concerns have been raised that subjecting the cells in the vicinity of the .sup.32 P stent to such low dose rates of radiation following implantation may not only be ineffective for restenosis prevention, but may even activate cellular proliferation.
Accordingly, it is desirable to have a new radioactive metallic stent and methods of preparing the same that overcome the disadvantages of the .sup.32 P stent. A stent that is loaded with a radioisotope that delivers radiation for a shorter period of time is desirable. A stent that is capable of delivering radioactivity at a dose rate of at least 10 cGy per hour during the first twelve hours to twelve days after the stent is implanted is also desirable. A method which is relatively simple and rapid and allows a predictable amount of radioactivity to be incorporated into stents of various lengths and types on the same day the stenting procedure is being performed is especially desirable.